The present invention relates to a novel method for the preparation of pre-filled plastic syringes, and preferably to the preparation of plastic syringes pre-filled with diagnostic contrast agents.
Plastic syringes, pre-filled with liquid or semi-solid materials suitable for diagnosis and/or treatment of medical conditions, find utility in the pharmaceutical arts. As can readily be appreciated, it is desirable that such syringes contain minimal amounts of pyrogens and viable and non-viable particulates.
Methods for preparing pre-filled plastic syringes have previously been disclosed. For example, U.S. Pat. No. 4,718,463 describes a method for the preparation of pre-filled plastic syringes comprising, among other steps, a step wherein the barrel of the syringe is washed with a multiplicity of jets of water to remove debris and pyrogens from the barrel, followed by assembly and filling of the syringe and a terminal autoclaving step wherein the filled syringe and its contents are sterilized.
The present invention provides a method for the preparation of a pre-filled plastic syringe, comprising the steps of:
(a) providing at least one component of said syringe which is molded under conditions which are substantially free of pyrogens and viable and non-viable particulates; and
(b) filling and assembling said syringe. Preferably, the syringe comprises as components a barrel, a tip seal capable of sealing the nozzle of the barrel and a piston capable of sliding in the barrel and sealing the open end of the barrel opposite the nozzle, and further, said at least one component in step (a) includes one or more of the barrel, the tip seal and/or the piston. Most preferably, said at least one component in step (a) includes at least the barrel of the syringe. The present invention also provides a novel method for molding a syringe component, such as a barrel, tip seal or piston, comprising the step of molding said component under conditions which are substantially free of pyrogens and viable and non-viable particulates.
The method of the present invention, wherein at least one of the aforementioned components, preferably at least the barrel, is molded under conditions which are substantially free of pyrogens and viable and non-viable particulates, allows the preparation of a pre-filled plastic syringe in a less cumbersome and more efficient manner than known methods by obviating the need for subsequent treatment steps such as water washing. Thus, while the component(s) molded under conditions which are substantially free of pyrogens and viable and non-viable particulates may optionally be treated subsequent to molding, such as by water washing, such subsequent steps may be omitted or reduced in intensity or duration by use of the present method.
Preferably, the component(s) molded under conditions which are substantially free of pyrogens and viable and non-viable particulates in accordance with step (a) are maintained under clean conditions until they are assembled in the syringe. In this regard, it is further preferred that clean conditions be maintained at least until the syringe is completely assembled (for example, that the partly assembled syringe be maintained under clean conditions). Thus, in a preferred embodiment, the present invention provides a method for the preparation of a pre-filled plastic syringe, wherein said syringe comprises the aforementioned barrel, tip seal and piston, comprising the steps of:
(a) (i) providing a barrel which is molded under conditions which are substantially free of pyrogens and viable and non-viable particulates, and, optionally, providing a tip seal and/or a piston which is also molded under conditions which are substantially free of pyrogens and viable and non-viable particulates; and
(ii) maintaining said barrel and, optionally, said tip seal and/or piston, under clean conditions for use in step (b); and
(b) filling and assembling said syringe.
In a particularly preferred embodiment, the present invention provides a method for the preparation of a pre-filled plastic syringe, wherein said syringe comprises the aforementioned barrel, tip seal and piston, comprising the steps of:
(a) (i) providing a barrel which is molded under conditions which are substantially free of pyrogens and viable and non-viable particulates, and, optionally, providing a tip seal and/or a piston which is also molded under conditions which are substantially free of pyrogens and viable and non-viable particulates; and
(ii) maintaining said barrel and, optionally, said tip seal and/or piston, under clean conditions for use in step (b); and
(b) filling and assembling said syringe, wherein:
(i) the tip seal is attached to the nozzle end of said barrel;
(ii) the barrel and tip seal assembly is filled with a liquid or semi-solid through the open end of the barrel, said open end being opposite said nozzle end of the barrel; and
(iii) the piston is assembled in said open end of the barrel; and
(c) optionally, sterilizing the assembled syringe and its contents.